Qiongqiong Yang

Renal pathological change in patients with type 2 diabetes is not always diabetic nephropathy: a report of 52 cases.

AIMS The present study examined the relationship between clinical features and renal histological changes in the Type 2-diabetic patients and evaluated the usefulness of renal biopsy in the diagnosis of diabetic versus non-diabetic kidney disease. METHODS 52 patients with Type 2-diabetic mellitus were retrospectively analyzed for differential clinical, laboratory features and pathological characteristics including overt proteinuria (> 0.5 g/day), elevated serum creatinine and/or the development of hematuria. RESULTS Of 52 patients, 20 cases (38.5%) showed no detectable diabetic lesions and, thus, were diagnosed as non-diabetic renal disease (NDRD), while 32 patients (61.5%) exhibited diabetic nephropathy. Interestingly, while 29 patients showed diabetic nephropathy (DN) alone, NDRD was also found in 3 patients with DN. Clinically, 24 out of 52 patients (46.16%) had a diagnosis consistent with the pathological findings, while 10 (19.23%) were diagnosed incorrectly. Compared to NDRD patients, patients with DN had prolonged diabetic history with or without retinopathy, while 25% of patients with NDRD exhibited mesangial proliferative glomerulonephritis. CONCLUSIONS NDRD was a common feature in Type 2-diabetic patients with renal involvement. The absence of retinopathy and short periods of diabetic history may be useful indicators for diagnosis of NDRD clinically.

Influence of dialysis modality on renal transplant complications and outcomes.

AIMS The present study investigated the influence of the pretransplant dialysis modality, hemodialysis (HD) or peritoneal dialysis (PD), on renal transplant complications and outcomes. METHODS 402 cadaveric renal transplant patients maintained on HD (N = 303) or PD (N = 99) for more than 3 months prior to transplantation were studied retrospectively, and a total of 345 patients were followed up for 30.2 +/- 15.2 months. The impact of HD or PD on acute rejection, delayed graft function (DGF), infection, chronic rejection, and the survival rate of graft and patients were analyzed. RESULTS There was no significant difference between the HD and PD groups with regard to the causes of end-stage renal disease, age, gender, blood pressure, hemoglobin, HLA match, hot and cold ischemia time, and hepatitis C virus infection. The incidence rates of DGF, acute rejection, chronic rejection and cytomegalovirus and other infections were also not significantly different between the HD and PD groups. However, compared to HD, patients with PD had longer dialysis duration (p < 0.05), but less hepatitis B infection (p < 0.05) and post-transplant infection (p < 0.05). In contrast, in those PD patients with hepatitis B infection, graft loss was significantly increased (19.23% vs. 8.86% , p = 0.021). The incidence of acute rejection episodes was higher in HD patients who had pretransplant dialysis for more than 12 months (p < 0.05). The overall patient and graft survival rates within 5 years between the HD and PD groups were not significantly different (p > 0.05). CONCLUSIONS The influence of PD and HD on complications after renal transplant at 1 year and 5 years and graft survival rates was similar, and therefore, either HD or PD can be chosen as the pretransplant dialysis modality. However, patients in the PD group had a reduced incidence of hepatitis virus infection, suggesting that PD may have certain advantages over HD as a preoperative substitution therapy for renal transplantation.

V-ATPase Promotes Transforming Growth Factor-β-induced Epithelial-Mesenchymal Transition of Rat Proximal Tubular Epithelial Cells

The ubiquitous vacuolar H(+)-ATPase (V-ATPase), a multisubunit proton pump, is essential for intraorganellar acidification. Here, we hypothesized that V-ATPase is involved in the pathogenesis of kidney tubulointerstitial fibrosis. We first examined its expression in the rat unilateral ureteral obstruction (UUO) model of kidney fibrosis and transforming growth factor (TGF)-β1-mediated epithelial-to-mesenchymal transition (EMT) in rat proximal tubular epithelial cells (NRK52E). Immunofluorescence experiments showed that UUO resulted in significant upregulation of V-ATPase subunits (B2, E, and c) and α-smooth muscle actin (α-SMA) in areas of tubulointerstitial injury. We further observed that TGF-β1 (10 ng/ml) treatment resulted in EMT of NRK52E (upregulation of α-SMA and downregulation of E-cadherin) in a time-dependent manner and significant upregulation of V-ATPase B2 and c subunits after 48 h and the E subunit after 24 h, by real-time PCR and immunoblot analyses. The ATP hydrolysis activity tested by an ATP/NADH-coupled assay was increased after 48-h TGF-β1 treatment. Using intracellular pH measurements with the SNARF-4F indicator, Na(+)-independent pH recovery was significantly faster after an NH(4)Cl pulse in 48-h TGF-β1-treated cells than controls. Furthermore, the V-ATPase inhibitor bafilomycin A1 partially protected the cells from EMT. TGF-β1 induced an increase in the cell surface expression of the B2 subunit, and small interfering RNA-mediated B2 subunit knockdown partially reduced the V-ATPase activity and attenuated EMT induced by TGF-β1. Together, these findings show that V-ATPase may promote EMT and chronic tubulointerstitial fibrosis due to increasing its activity by either overexpression or redistribution of its subunits.

Is cystatin C a better marker than creatinine for evaluating residual renal function in patients on continuous ambulatory peritoneal dialysis

BACKGROUND Current clinical assessments of residual renal function (RRF) for continuous ambulatory peritoneal dialysis (CAPD) patients usually require 24 h of urine collection, which is sometimes difficult for patients and contributes to random errors. Objective. Our study aims to investigate whether serum cystatin C (CysC) can serve as a better marker of RRF than serum creatinine (Cr) in CAPD and to develop a formula to estimate RRF with CysC levels. METHODS One hundred and sixty CAPD patients from a single dialysis unit were randomly divided into modeling (n(1) = 120) and validation (n(2) = 40) groups. RRF was assessed as the average of the renal clearances of urea and creatinine. We then derived RRF formulas based on the CysC and Cr levels from the modeling group and validated them by comparison with a published CysC-based equation and Modification of Diet in Renal Disease formula. RESULTS CysC levels were inversely related to RRF, Kt/V(urea) and total weekly Ccr but were unrelated to age, gender, body mass index, diabetes or peritoneal clearance. The RRF formulas derived from CysC and Cr were (sinh(ln(6.736-0.566 CysC)))(2) and (sinh(ln(6.097-0.265 Cr)))(2), respectively. When applied to the validation group, the estimated RRF based on CysC (2.8 ± 1.2 mL/min/1.73 m(2)) was similar to that of on Cr (2.8 ± 1.3 mL/min/1.73 m(2)) and the measured RRF (2.9 ± 1.7 mL/min/1.73 m(2)). The CysC formula showed a small bias, with the best 30 and 50% accuracy and had a larger area under the curve and higher sensitivity and specificity when compared to the Cr formula and other formulas. CONCLUSION Serum CysC may be a good marker for the estimation of RRF in CAPD patients. The derived CysC formula may be used to reliably estimate RRF in CAPD patients without the need for collection of 24 h urine.

Clinicopathologic features and treatment response in nephrotic IgA nephropathy with minimal change disease.

OBJECTIVE To analyze the clinicopathological features and therapeutic response of nephrotic IgA nephropathy (IgAN) patients with minimal-change disease (MCD). METHODS 62 nephrotic IgAN patients were enrolled between January 2002 and December 2008, and divided into two groups including Group A: patients with MCD-like pathological features, and Group B with non-MCD pathologic pattern. The clinicopathological features, treatments, and responses were then analyzed. RESULTS 13 (21.0%) patients exhibited MCD-like pathological changes. Patients in Group A presented more prominent proteinuria, hypoalbuminemia but higher hemoglobin and no incidence of renal insufficiency compared to Group B (p < 0.05). 62 patients were treated with corticosteroid, and the complete remission rate in Group A is higher than that in Group B (84.6% vs. 34.7%, p = 0.008), but the relapse rate is much higher in Group A (53.8% vs. 20.4%, p = 0.03). 21 patients were treated combining with immunosuppressant due to unresponsiveness or relapse, which yielded a high re-remission rate in Group A (100%). After follow-up of 53.9 ± 26.9 months, the 5-year renal survival rate is higher in Group A (100%) than that in Group B (84.7%), but no significant difference was observed (p = 0.24). CONCLUSIONS MCD-like pathological changes exist in quite a few nephrotic IgAN patients. These IgAN patients responded well to corticosteroid monotherapy but had a higher rate of relapse. Though manifesting with severe nephrotic symptoms, they tended to have a favorable clinical outcome probably due to the minimal pathological changes. Nevertheless, larger sample size and longer follow-up periods are needed for better understanding of the disease.

Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury.

Abstract Objective: The aim of this work is to investigate the distinctive clinicopathological characteristics of AKI in Chinese IgAN population and possible risk factors for AKI. Methods: We performed a retrospective analysis of 1512 patients with biopsy-proven primary IgAN in the period 2006 through 2011 in The First Affiliated Hospital of Sun Yat-sen University. AKI was defined as 2012 KDIGO (Kidney Diseases: Improving Global Outcomes) criteria, and the patients were divided into AKI group (n = 145) and non-AKI group (n = 1367). Results: The prevalence of AKI of the IgAN patients in our center was 9.59% (145/1512). Most AKI patients were older age, male, with higher percentage of smoke, hypertension, hyperlipidemia and preexisting impaired kidney function (Scr > 133 μmol/L), and higher serum creatinine, proteinuria, uric acid, whilst less onset of macroscopic hematuria as well as lower serum albumin and hemoglobin (p < 0.05). The pathological features were much more severe in AKI group as well. Acute tubulointerstitial nephritis was found as the most predominant pathological change of intrinsic AKI in our IgAN population instead of macroscopic hematuria associated acute tubular injury/necrosis. In multivariate logistic regression analysis, we found that older age, male gender, malignant hypertension, proteinuria, cellular crescent, fibrocellular crescent, glomerular sclerosis ≥ 50% were possible risk factors for AKI. Conclusions: AKI is commonly seen among IgAN population. The clinicopathological features are much more severe in IgAN patients with AKI. Useful clinicopathological predictors are recognized to improve the identification of IgAN patients who are at high risk for AKI.

Clinical outcomes of IgA nephropathy patients with different proportions of crescents

Abstract Crescents involving more than 50% of glomeruli in IgA nephropathy (IgAN) signify a rapid deterioration of renal function. However, little is known about the prognosis of IgAN patients presenting crescents in less than 50% of glomeruli. We aimed to investigate the clinicopathological characteristics and outcomes of IgAN patients with different proportions of crescents. From January 2000 to December 2011, biopsy-proven primary IgAN patients with histological crescents formation were enrolled in this retrospective cohort study. The patients were divided into 4 groups on the basis of crescent proportion as follows: <5%, 5% to 9%, 10% to 24%, and ≥25%. The primary endpoint was defined as the doubling of baseline serum creatinine (SCr) and/or end-stage renal disease (ESRD), and the secondary endpoint was death. A total of 538 crescent-featured IgAN patients were followed up and included in the analysis. The median crescent proportion was 8.0%. An increasing crescent proportion was associated with a reduced estimated glomerular filtration rate (eGFR), decreased level of hemoglobin, and increased amount of urine protein excretion. After a median follow-up period of 51 months (range 12–154 months), the endpoint events-free survival rate of the above 4 groups were 69.9%, 47.7%, 43.8%, and 40.6%, respectively (Log rank=13.7, P= 0.003), when we incorporated death with renal outcome as a composite endpoint. Multivariate Cox regression analyses adjusting for eGFR, hypertension, proteinuria, and the Oxford-MEST classification demonstrated the predictive significance of an increasing crescent proportion with renal survival and mortality (each increase by 5% [log-transformed]: HR=1.51, 95% CI 1.08–2.11, P = 0.02). Further comparisons of patients with small proportions of crescents (<5%) and those absent of such pathological lesion showed that the 2 groups of patients had comparable prognosis. An increasing crescent proportion was identified as an independent predictor for unfavorable clinical outcomes in IgAN. Therefore, a small proportion of crescents, over 5% particularly, should be paid more attention in clinical practice.

Interaction between V-ATPase B2 and (Pro) renin Receptors in Promoting the progression of Renal Tubulointerstitial Fibrosis

To investigate the levels of (Pro) renin receptor [(P) RR], α-smooth muscle actin (α-SMA), fibronectin (FN), and vacuolar H+-ATPase (V-ATPase) subunits (B2, E, and c) in rat unilateral ureteral obstruction (UUO) models and rat proximal tubular epithelial cells (NRK-52E) treated with prorenin to elucidate the role of V-ATPase in these processes by activating the (P) RR. UUO significantly upregulated (P) RR, V-ATPase subunits, α-SMA and FN expression in tubulointerstitium or tubular epithelial cells. A marked colocalization of (P) RR and the B2 subunit was also observed. Prorenin treatment upregulated α-SMA, FN, (P) RR, and V-ATPase subunits and activity in NRK52E cell in a dose- and time-dependent manner. The V-ATPase inhibitor bafilomycin A1 partially blocked prorenin-induced (P) RR, FN, and α-SMA expression. Co-immunoprecipitate and immunofluorescence results demonstrated that the V-ATPase B2 subunit bound to the (P) RR, which was upregulated after prorenin stimulation. Either siRNA-mediated (P) RR or B2 subunit knockdown partially reduced V-ATPase activity and attenuated prorenin-induced FN and α-SMA expression. From the data we can assume that activation of (P) RR and V-ATPase may play an important role in tubulointerstitial fibrosis with possible involvement of interaction of V-ATPase B2 subunit and (P)RR.

Hepatitis B Virus Infection Rate and Distribution in Chinese Systemic Lupus Erythematosus Patients

Background The aim of this study was to investigate the hepatitis B virus (HBV) infection rate in systemic lupus erythematosus (SLE) patients in China, and to determine the age and sex distribution. Material/Methods A total of 3981 SLE patients diagnosed in The First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2011 were retrospectively investigated for evaluation of the HBV infection rate. The HBV infection rate and the positive rate of hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) were standardized to national census data in 2000 and compared with the prevalence found in the 2006 national survey. Results The age and sex standardized HBV infection rate in Chinese SLE patients was 3.3%. The age and sex standardized positive rate of HBsAb and HBcAb were 58.1% and 26.1%, respectively. As compared with the prevalence from the 2006 national survey, the HBV infection rate and the positive rate of HBcAb were lower and the positive rate of HBsAb was higher in SLE patients aged 15–49 years old compared to peers in the general population. There was no difference in HBV infection rate between males and females (4.2% vs. 2.8%, p=0.088) in SLE patients. Conclusions The HBV infection rate was relatively lower in SLE patients compared with the general population, but there was no difference in pediatric patients or patients aged above 50 years old. Unlike in the general population, the HBV infection rate had no statistical differences between males and females in SLE patients.

Baseline higher peritoneal transport had been associated with worse nutritional status of incident continuous ambulatory peritoneal dialysis patients in Southern China: a 1-year prospective study.

The aim of the present study was to investigate the relationship between baseline peritoneal transport types and nutritional status in Chinese continuous ambulatory peritoneal dialysis (CAPD) patients. In the present single-centre, prospective study, incident CAPD patients were included from 15 April 2010 to 31 December 2011 and were followed up for 12 months. According to the results of baseline peritoneal equilibration test, patients were divided into lower peritoneal transport group (lower transporters) and higher peritoneal transport group (higher transporters). Nutritional status was evaluated by both subjective global assessment (SGA) and protein-energy wasting (PEW) score. The body composition parameters were assessed by body impedance analysis. A total of 283 CAPD patients were included in the study, of which 171 (60.4 %) were males with a mean age of 47.0 (sd 14.9) years. Compared with lower transporters (n 92), higher transporters (n 181) had lower levels of serum albumin (37.1 (sd 4.3) v. 39.6 (sd 4.3) g/l, P< 0.001), serum pre-albumin (356 (sd 99) v. 384 (sd 90) mg/l, P= 0.035), phase angle (6.15 (sd 0.39) v. 6.27 (sd 0.47)°, P< 0.05) and higher rate of malnutrition defined by SGA (52.5 v. 25.0%, P< 0.001) and PEW score (37.0 v. 14.1 %, P< 0.001) at 1-year of follow-up. Baseline higher peritoneal transport, analysed by multivariate binary logistic regressions, was independently associated with malnutrition (SGA mild to moderate and severe malnutrition: OR 3.43, 95% CI 1.69, 6.96, P< 0.01; PEW: OR 2.40, 95% CI 1.08, 5.31, P= 0.03). It was concluded that baseline higher peritoneal transport was independently associated with worse nutritional status of CAPD patients in Southern China.